Suppressive activity of a macrolide antibiotic, roxithromycin, on pro-inflammatory cytokine production in vitro and in vivo.

This study was designed to examine the influence of a macrolide antibiotic, roxithromycin (RXM), on the production of pro-inflammatory cytokines, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. In the first experiments, we examined the effect of RXM on in vitro cytokine production from lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes. The monocytes were cultured in the presence of various doses of the agent. After 24 h, the culture supernatants were obtained and assayed for IL-1beta and TNF-alpha contents by enzyme-linked immunosorbent assay. RXM suppressed the in vitro production of IL-1beta and TNF-alpha in response to LPS stimulation. This was dose dependent and first noted at a concentration of as little as 0.05 microg/ml, which is much lower than therapeutic blood levels. In the second part of the experiments, we examined the influence of RXM on the appearance of IL-1beta and TNF-alpha in mouse lung extract induced by LPS inhalation. RXM was administered orally into BALB/c mice at a single dose of 2.5 mg/kg once a day for 5-12 weeks. These mice were then instilled with LPS into the trachea and examined for the presence of cytokines in aqueous lung extracts. Pretreatment of mice with RXM for 5 weeks did not influence of the appearance of both IL-1beta and TNF-alpha in aqueous lung extracts. However, pretreatment for more than 7 weeks dramatically suppressed the cytokine appearance in the extracts

Inhibition of Angiogenic Factor Production from Murine Mast Cells by an Antiallergic Agent (Epinastine Hydrochloride) In Vitro

Angiogenesis is an important event both in the development of allergic inflammatory responses and in the pathophysiology of tissue remodeling in allergic diseases. In the present study, therefore, we examined the influence of antihistamines on angiogenesis through the choice of epinastine hydrochloride (EP) and murine mast cells in vitro. Mast cells (5 × 105 cells/mL) presensitized with murine IgE specific for ovalbumin (OVA) were stimulated with 10 ng/mL OVA in the presence of various concentrations of EP for 4 hours. The levels of angiogenesis factors, keratinocyte-derived chemokine (KC), tumor necrosis factor-α (TNF), and vascular endothelial growth factor (VEGF) in culture supernatants, were examined by ELISA. We also examined mRNA expression for the angiogenesis factors by RT-PCR. EP significantly inhibited the production of KC, TNF, and VEGF induced by IgE-dependent mechanism at more than 25 ng/mL. Semiquantitative analysis using RT-PCR showed that EP also significantly reduced mRNA expressions for KC, TNF, and VEGF. These results strongly suggest that EP suppresses angiogenesis factor production through the inhibition of mRNA expression in mast cells and results in favorable modification of clinical conditions of allergic diseases

Influence of a macrolide antibiotic, roxithromycin, on mast cell growth and activation in vitro.

BACKGROUND: Long-term administration of macrolide antibiotics is recognized to be able to favorably modify the clinical condition of inflammatory diseases, such as diffuse panbronchiolitis and cystic fibrosis. However, the precise mechanisms by which macrolide antibiotics could improve clinical conditions of the patients are not well understood. AIM: The present study was designed to examine the influence of macrolide antibiotics on effector cell functions responsible for inflammation through the choice of roxithromycin (RXM) and mast cell. METHODS: Mast cells were induced by long-term culture of splenocytes from BALB/c mice. RXM was added to the cultures at seeding and then every 4-5 days, when the culture medium was replaced with a fresh one. The influence of RXM on mast cell growth was evaluated by counting the number of cells grown on the 16th day. We also examined the influence of RXM on mast cell activation by examining histamine release and inflammatory cytokine secretion. RESULTS AND CONCLUSION: RXM could not inhibit mast cell growth, even when splenocytes were exposed to 100 microg/ml of RXM throughout the entire culture periods. RXM also could not suppress histamine release from cultured mast cells in response to non-immunological and immunological stimulations. However, RXM could suppress inflammatory cytokine, interleukin-1beta, interleukin-6, granulocyte macrophage-colony stimulating factor and tumor necrosis factor-alpha, secretions induced by concanavalin A stimulation at a concentration of as little as 0.5 microg/ml. These results may suggest that RXM modulated the ability of mast cells to secrete inflammatory cytokines and results in improvement of clinical condition of chronic inflammatory diseases

Suppressive effects of co-stimulatory molecule expressions on mouse splenocytes by anti-allergic agents in vitro.

The influence of anti-allergic drugs, epinastine hydrochloride (EP) and disodium cromoglycate (DSCG), on the co-stimulatory molecule expression was examined using in vitro cell culture technique. Spleen cells obtained from BALB/c mice 10 days after immunization with haemocyanin absorbed to aluminium hydroxide were cultured in the presence of 100.0 microg/ml haemocyanin and various concentrations of the agents. Low concentrations (<1.5 x 10(-4)M) of EP and DSCG did not influence spleen cell blastic activity induced by antigenic stimulation, whereas these agents caused significant inhibition of spleen cell activation when 2 x 10(-4) M of the agents were added to cell cultures. EP and DSCG also did not affect blastic activity of sensitized splenic T cells by anti-CD3 monoclonal antibody stimulation even when these cells were cultured in the presence of 2 x 10(-4) M of the agents. We next examined the influence of EP and DSCG on the expression of co-stimulatory molecules on spleen cells in response to antigenic stimulation. Sensitized spleen cells were cultured in the presence of 2 x 10(-4)M of the agents and the expression of molecules were examined by flow cytometer 24h later. EP and DSCG suppressed the expression of costimulatory molecules, CD40 and CD80, but not CD86, on splenic B cells which were enhanced by antigenic stimulation in vitro

Polyandry and fitness in female horned flour beetles, Gnatocerus cornutus

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Although polyandry is common, it is often unclear why females mate with multiple males, because although polyandry may provide females with direct or indirect fitness benefits, it can also be costly. Our understanding of polyandry is also restricted by the relative paucity of studies that disentangle the fitness effects of mating more than once with a single male and mating with multiple males. Here we investigated potential benefits and costs of polyandry in the horned beetle, Gnatocerus cornutus, while controlling for the number of matings. We found that female life span was independent of mating frequency, indicating that mating itself is not very costly. However, females that mated more than once laid more eggs and had greater lifetime reproductive success than singly mated females. Because the magnitude of these effects was similar in monandrous and polyandrous females, this improved fertility was due to multiple mating itself, rather than mating with multiple males. However, although polyandrous females produced more attractive sons, these males tended to have smaller mandibles and so may fare less well in male-male competition. The se results indicate that polyandry is relatively cost free, at least in the laboratory, and has direct and indirect benefits to female fitness. However, because the attractive sons produced by polyandrous females may fight less well, the indirect benefits of polyandry will depend on the intensity of male-male competition and how free females are to exert mate choice. Where competition between males is intense, polyandry benefits via son attractiveness may be reduced and perhaps even carry costs to female fitness.This study was supported by a Grant-in-Aid for Scientific Research (KAKENHI 25840157) from Japanese Ministry of Education, Science, Sports and Culture. We thank the Editor and referees for helpful comments which greatly improved the manuscript

Optical cavity with a double-layered cholesteric liquid crystal mirror and its prospective application to solid state laser

The authors have fabricated an optical cavity with silver (Ag) and double-layered cholesteric liquid crystal (CLC) mirrors facing each other. This CLC mirror consists of left-handed CLC and right-handed CLC films for high light reflection irrespective of polarization states. A single-mode lasing was observed in dye-doped CLC sandwiched between Ag and double-layered CLC mirrors. The authors also fabricated a flexible solid state device with a spin-coated dye molecular film sandwiched between Ag and double-layered CLC mirrors. Amplified spontaneous emission was observed from the solid state device, suggesting a possible structure for a flexible and tunable solid state laser.open

Extended Generalized Feistel Networks using Matrix Representation

International audienceWhile Generalized Feistel Networks have been widely studied in the literature as a building block of a block cipher, we propose in this paper a unified vision to easily represent them through a matrix representation. We then propose a new class of such schemes called Extended Generalized Feistel Networks well suited for cryptographic applications. We instantiate those proposals into two particular constructions and we finally analyze their security

An Enigmatic Stramenopile Sheds Light on Early Evolution in Ochrophyta Plastid Organellogenesis

Ochrophyta is an algal group belonging to the Stramenopiles and comprises diverse lineages of algae which contribute significantly to the oceanic ecosystems as primary producers. However, early evolution of the plastid organelle in Ochrophyta is not fully understood. In this study, we provide a well-supported tree of the Stramenopiles inferred by the large-scale phylogenomic analysis that unveils the eukaryvorous (nonphotosynthetic) protist Actinophrys sol (Actinophryidae) is closely related to Ochrophyta. We used genomic and transcriptomic data generated from A. sol to detect molecular traits of its plastid and we found no evidence of plastid genome and plastid-mediated biosynthesis, consistent with previous ultrastructural studies that did not identify any plastids in Actinophryidae. Moreover, our phylogenetic analyses of particular biosynthetic pathways provide no evidence of a current and past plastid in A. sol. However, we found more than a dozen organellar aminoacyl-tRNA synthases (aaRSs) that are of algal origin. Close relationships between aaRS from A. sol and their ochrophyte homologs document gene transfer of algal genes that happened before the divergence of Actinophryidae and Ochrophyta lineages. We further showed experimentally that organellar aaRSs of A. sol are targeted exclusively to mitochondria, although organellar aaRSs in Ochrophyta are dually targeted to mitochondria and plastids. Together, our findings suggested that the last common ancestor of Actinophryidae and Ochrophyta had not yet completed the establishment of host–plastid partnership as seen in the current Ochrophyta species, but acquired at least certain nuclear-encoded genes for the plastid functions

Impossible Differential Cryptanalysis of Reduced-Round Tweakable TWINE

Tweakable TWINE (T-TWINE) is a new lightweight tweakable block cipher family proposed by Sakamoto $et$ $al$. at IWSEC 2019. T-TWINE is the first Tweakable Block Cipher (TBC) that is built on Generalized Feistel Structure (GFS). It is based on the TWINE block cipher in addition to a simple tweak scheduling based on SKINNY’s tweakey schedule. Similar to TWINE, it has two versions, namely, T-TWINE-80 and T-TWINE-128, both have a block length of 64 bits and employ keys of length 80 and 128 bits, respectively. In this paper, we present impossible differential attacks against reduced-round versions of T-TWINE-80 and T-TWINE-128. First, we present an 18-round impossible differential distinguisher against T-TWINE. Then, using this distinguisher, we attack 25 and 27 rounds of T-TWINE-80 and T-TWINE-128, respectively